Review Reports - Oxidative Hydroxylation of Aryl Boronic Acid Catalyzed by Co-porphyrin Complexes via Blue-Light Irradiation

Round 1

Reviewer 1 Report

The manuscript describes an interesting and potentially useful route to phenols via a mild route which follows some of the precepts of green chemistry and in this way "eco-friendly" claim is somewhat justified. However, this term is not easily applicable to the usual routes to boronic acids so this should be borne in mind when using these arguments to support the significance of the work being reported. The results are rather limited in terms of the number substrates examined but are adequate for a preliminary communication and the yields from the reaction are good. It is not clear why the authors have chosen a catalyst loading of 0.3mol% and studies describing the optimisation of this value, if available, should also be included. Also, the authors describe an immobilised catalyst and refer to the fact that it could be reusable. The authors may wish to revise the text here since such a claim should be supported by appropriate studies involving the recovery of the catalyst and its use in successive catalytic cycles, together with an assessment of the amount of catalyst leaching that occurs through repeated use.

If the above observations can be dealt with in some way, then the manuscript can considered suitable for publication as a short preliminary communication. In addition to the above, there are a number of errors which have been identified and should be corrected:

line 24: PhI is not an oxidant. According to the cited reference this should be corrected to PhI(OAc)₂
line 41: "ligand" should be replaced by "catalyst"
line 43: insert "under" before "aerobic"
lines 43-44: The meaning "including radical-chain mechanisms" is not clear in the context of the sentence. Maybe better to replace "including" by "possibly via"
line 51: "the most attention" is disputable. Suggest replacement by "much attention"
line 60: The authors claim to have developed oxidative reactions "without oxidizing agents" which is somewhat remarkable. This phrase should be deleted.
line 61: "under the atmosphere" is incorrect since it does not necessarily imply an aerobic atmosphere. The normal expression to be used here is simply "in air".
line 68: change "to the atmosphere" to "to air"
line 78: change "under the atmosphere" to "in air"
line 103: change "on air" to "in air"
lines 108-109: The sentence "p-Bromophenyl boronic acid was tolerated etc" is not clearly formulated. Presumably the authors want to say that the oxidation proceeds without any observable debromination?
line 110: change "at a" to "in"
line 112: change "under the atmosphere without any oxidizing agent" to "in air without any additional oxidizing agent"
line 144: change "under the atmosphere" to "in air"
line 145: Correct "Purple crystal was" to "Purple crystals were"
line 171: correct "peroxydisulfaite" to "peroxydisulfate"
line 184: change "would" to "could"

Author Response

Reviewer 1:

Q1. The manuscript describes an interesting and potentially useful route to phenols via a mild route which follows some of the precepts of green chemistry and in this way "eco-friendly" claim is somewhat justified. However, this term is not easily applicable to the usual routes to boronic acids so this should be borne in mind when using these arguments to support the significance of the work being reported.

A1. In the revised manuscript, we added more examples of our reactions as eco-friendly way that it doesn’t release waste oxidants or by-products into the atmosphere. We used molecular oxygen from the atmosphere in addition to using water as solvent and porphyrin as more environmental catalyst. Porphyrin/polyaniline complex could be removed from the reaction medium by filtration. From this point of view, we added some potential possibilities and related advantages using porphyrin/polyaniline and chitosan metal-complexes. Additionally written changes are highlighted in yellow background in the revised text. (line 53-60)

Q2. The results are rather limited in terms of the number substrates examined but are adequate for a preliminary communication and the yields from the reaction are good.

A2. Different types of substitutes were studied and the results showed that the arylboronic acids with electron-donating and electron-withdrawing substituents gave the corresponding phenols within a varying reaction time 4-6 h. Methylated, trimethylated, halogenated phenyl boronic acids and a bulk substrate such as 1-naphthalene boronic acid were converted to form the corresponding oxidized products in excellent yields by Co^II-TCPP supported on polyaniline. Also the reactions were underwent in different kinds of solvents and mediums, and we made comparison with other porphyrins.

Q3. It is not clear why the authors have chosen a catalyst loading of 0.3mol% and studies describing the optimisation of this value, if available, should also be included.

A3. 0.2 mol% of Co(II) porphyrin catalyst provided the desired product in 30% yield under similar conditions, so that the concentration should be increased until the higher yield of 0.3 mol% catalyst loading. Higher concentration of porphyrin more than 0.3 mol% would cause to decrease in the adsorption of other staring material on the polymer surface due to the aggregation of porphyrin. When the concentration of Co(II) porphyrin catalyst increases as the aggregation form of porphyrin, it seems to be less reactive than the monomeric form. These explanation was added to the revised manuscript. (line 128-133)

Q4. Also, the authors describe an immobilised catalyst and refer to the fact that it could be reusable. The authors may wish to revise the text here since such a claim should be supported by appropriate studies involving the recovery of the catalyst and its use in successive catalytic cycles, together with an assessment of the amount of catalyst leaching that occurs through repeated use.

A4. Re-use of the catalyst Co(II)TCPP supported on polyaniline was tested as follows. Hydroxylation of phenylboronic acid was carried out under standard conditions of Table 1, after the completion of the first run the solvent was removed by filtration and the product was isolated and determined by NMR measurements. The precipitate (Co-porphyrin supported on polyaniline) could be washed with water and used for the second time by added the initial amount of phenylboronic acid, TEA and solvent, then the reaction was carried out at room temperature for 6 h to give 40 % of the product. After two runs we found that the re-use of the catalyst activity is less than the fresh catalyst. The deactivation of the catalyst could be due to the accumulation of the reaction products and porphyrin in the polymer. Although we couldn’t find a practical re-usable catalytic method, we improve the yields by finding suitable solvent for isolating the product and these results would be disclosed as a full paper in near future.

Q5. If the above observations can be dealt with in some way, then the manuscript can considered suitable for publication as a short preliminary communication. In addition to the above, there are a number of errors which have been identified and should be corrected:

A5. Some errors which have been identified ware corrected in the revised manuscript as follows:

line 24: PhI is not an oxidant. According to the cited reference this should be corrected to PhI(OAc)₂

“PhI” was changed to “hyper valent iodine” (line 24)

line 41: "ligand" should be replaced by "catalyst"

“Ligand” was changed to “catalyst” (line 48)

line 43: insert "under" before "aerobic"

“Under” was added before “aerobic” (line 50)

lines 43-44: The meaning "including radical-chain mechanisms" is not clear in the context of the sentence. Maybe better to replace "including" by "possibly via"

“including” was replaced by “possibly via” (line 50)

line 51: "the most attention" is disputable. Suggest replacement by "much attention"

“the most attention” was changed to “much attention” (line 65)

line 60: The authors claim to have developed oxidative reactions "without oxidizing agents" which is somewhat remarkable. This phrase should be deleted.

“Without oxidizing agents“ was changed to “under blue-light irradiation” (line 77)

line 61: "under the atmosphere" is incorrect since it does not necessarily imply an aerobic atmosphere. The normal expression to be used here is simply "in air".

“Under the atmosphere” was changed to “in air” (line 78)

line 68: change "to the atmosphere" to "to air"

“to the atmosphere” wsa changed to “to air” (line 98)

line 78: change "under the atmosphere" to "in air"

“Under the atmosphere” was changed to “in air” (line 108)

line 103: change "on air" to "in air"

“on air” was changed to “in air” (line 182)

lines 108-109: The sentence "p-Bromophenyl boronic acid was tolerated etc" is not clearly formulated. Presumably the authors want to say that the oxidation proceeds without any observable debromination?

The blue light has no effect on bromophenylboronic acid so it can give the product without decomposition. In the revised version, the sentence was changed as follows: “p-Bromophenyl boronic acid was tolerated to form the oxidized product, and the hydroxylation reaction proceeds without any observable debromination under blue-light irradiation.” (line 189)

line 110: change "at a" to "in"

“at a” was changed to “in” (line 191)

line 112: change "under the atmosphere without any oxidizing agent" to "in air without any additional oxidizing agent"

“under the atmosphere” was changed to “in air” (line 193)

line 144: change "under the atmosphere" to "in air"

“Under the atmosphere” was changed to “in air” (line 220)

line 145: Correct "Purple crystal was" to "Purple crystals were"

“purple crystal was” was change to “purple crystals were” (line 244)

line 171: correct "peroxydisulfaite" to "peroxydisulfate"

“peroxydisulfaite” was corrected to “peroxydisulfate” (line 274)

line 184: change "would" to "could"

“would” was changed to “could” (line 300)

Author Response File: Author Response.pdf

Reviewer 2 Report

Dear Editor,

Kimura and Atia reported an interesting synthesis of phenols by photoredox oxidation of the corresponding arylboronic acids.

The catalyst adopted for this transformation is based on cobalt porphyrins and the reaction proceeds under very mild condition using atmospheric oxygen as terminal oxidant for the transformation.

The use of cobalt porphyrin complexes in photocatalysis is well-documented in the literature. The reaction approach is quite similar to the one reported for other photocatalysts (e.g.: DOI: 10.1002/anie.201107028) but the use of cobalt complexes in this chemistry transformation is worth mentioning.

In my opinion the work reported in this manuscript is suitable for publication in catalysts after a minor revision.

Best Regards

In the first phrase of the introduction different methodologies for the oxidation in organic synthesis were reported. Please add some references for each methodology reported or a reference to a review about the topic. Furthermore, the use of iodobenzene as oxidant was reported, are you considered hypervalent iodine compounds such as PhI(OAc)2 or simple iodobenzene?
Page 2 line 52: “These methods depend on metal complexes with photosensitizers to engage in a single-electron transfer (SET) for photoexcitation processes under irradiation of visible light.” Nowadays photoredox catalysis employed also organic dyes as photoredox catalysts (with application also in the oxidation of boronic acids). Please consider also this type of photocatalyst and add some references: DOI: 10.1021/acs.chemrev.6b00057; DOI: dx.doi.org/10.1021/ja406311g and references below.
Page 2 line 60: “In this context, we developed oxidative reactions catalyzed by Co(II)-porphyrin without oxidizing agents to form useful molecules.”. The phrase is not properly correct. In fact, an oxidizing agent was employed in the reaction, the oxygen present in the air. Please revise the phrase.
Page 2 line 71: “In the absence of a catalyst and oxidizing agents…” see previous point.
The use of TEA as sacrificial reductant for the photocatalyst is clearly evinced in the text (page 2 line 74). Please reinforce this part of the text with a discussion about its use.
Page 3 line 94. Please comment the results obtained also consider the other methodologies reported in the references below, where H2O2 as not employed as oxidant.
Page 4 line 118-121: Please change “activated Co(II)-porphyrin” with Co(II)-porphyrin in its excited state”. In this case a SET event is responsible of the reduction of the Co(II) to Co(I)not an energy transfer event, correct the phrase.
Is it possible to recover the solid supported catalyst and reuse it in further reaction? Please add a test using recovered catalyst and add a comment in the text.
Please report in the main text a detailed experimental procedure for the photoredox oxidation of boronic acid
Some references were missed:
- DOI: 10.1021/ja406311g
- DOI: 10.1039/C8QO00061A
- DOI: 10.1021/acs.joc.7b00487
- DOI: 10.1039/c5cc01519g
- DOI: 10.1039/c3ob42081g
- DOI: 10.1002/anie.201107028
- 3762/bjoc.16.83
Please add emission profile of the light source used for irradiation of the reaction mixture

Author Response

Reviewer 2:

Kimura and Atia reported an interesting synthesis of phenols by photoredox oxidation of the corresponding arylboronic acids. The catalyst adopted for this transformation is based on cobalt porphyrins and the reaction proceeds under very mild condition using atmospheric oxygen as terminal oxidant for the transformation.

In my opinion the work reported in this manuscript is suitable for publication in catalysts after a minor revision.

Q1. In the first phrase of the introduction different methodologies for the oxidation in organic synthesis were reported. Please add some references for each methodology reported or a reference to a review about the topic.

A1. The references suggested by the referee were cited as references No. 1-5 in the revised version.

Q2. Furthermore, the use of iodobenzene as oxidant was reported, are you considered hypervalent iodine compounds such as PhI(OAc)₂ or simple iodobenzene?

A2. “PhI” was changed to “hyper valent Iodine”, in the revised text. (line 24)

Q3. Page 2 line 52: “These methods depend on metal complexes with photosensitizers to engage in a single-electron transfer (SET) for photoexcitation processes under irradiation of visible light.” Nowadays photoredox catalysis employed also organic dyes as photoredox catalysts (with application also in the oxidation of boronic acids). Please consider also this type of photocatalyst and add some references: DOI:10.1021/acs.chemrev.6b00057; DOI:dx.doi.org/10.1021/ja406311g and references below.

A3. The references suggested by the referee were cited as references No. 6-8 in the revised version.

Q4. Page 2 line 60: “In this context, we developed oxidative reactions catalyzed by Co(II)-porphyrin without oxidizing agents to form useful molecules.”. The phrase is not properly correct. In fact, an oxidizing agent was employed in the reaction, the oxygen present in the air. Please revise the phrase.

A4. In the revised text, the pointed sentence was chaged as follows: “We developed oxidative reactions catalyzed by Co(II)-porphyrin under blue-light irradiation to form useful molecules”. (line 77)

Q5. Page 2 line 71: “In the absence of a catalyst and oxidizing agents…” see previous point.

A5. The suggested sentence was chaged as follows: “In the absence of a catalyst and additives…”(line 101)

Q6. The use of TEA as sacrificial reductant for the photocatalyst is clearly evinced in the text (page 2 line 74). Please reinforce this part of the text with a discussion about its use.

A6. In the revised text, the pointed sentence was chaged as follows: “No reaction occurred in the absence of TEA as it is responsible for energy transfer from the activated Co(II)-porphyrin species as an electron donor to form a Co(I)-porphyrin species.” (line 109)

Q7. Page 3 line 94. Please comment the results obtained also consider the other methodologies reported in the references below, where H₂O₂ as not employed as oxidant.

A7. The references suggested by the referee were cited as references No. 11-12 in the revised version.

Q8. Page 4 line 118-121: Please change “activated Co(II)-porphyrin” with Co(II)-porphyrin in its excited state”. In this case a SET event is responsible of the reduction of the Co(II) to Co(I) not an energy transfer event, correct the phrase.

A8. In the revised text, the pointed sentence was chaged as follows: “Energy transfer from the Co(II)-porphyrin in its excited state species with triethylamine as an electron donor causes to form a Co(I)-porphyrin species.” (line 216)

Q9. Is it possible to recover the solid supported catalyst and reuse it in further reaction? Please add a test using recovered catalyst and add a comment in the text.

A9. Re-use of the catalyst Co(II)TCPP supported on polyaniline was tested as follows. Hydroxylation of phenylboronic acid was carried out under standard conditions of Table 1, after the completion of the first run the solvent was removed by filtration and the product was isolated and determined by NMR measurements. The precipitate (Co-porphyrin supported on polyaniline) could be washed with water and used for the second time by added the initial amount of phenylboronic acid, TEA and solvent, then the reaction was carried out at room temperature for 6 h to give 40 % of the product. After two runs we found that the re-use of the catalyst activity is less than the fresh catalyst. The deactivation of the catalyst could be due to the accumulation of the reaction products and porphyrin in the polymer. These sentences are added in the supporting information.

Q10. Please report in the main text a detailed experimental procedure for the photoredox oxidation of boronic acid.

A10. The following experimental procedures were revised in the revised manuscript. (line 282-292)

General method for hydroxylation reaction

Hydroxylation reaction catalysed by Co(II)TPP, Co(II)TMCPP,Co(II)TCPP.

A mixture of arylboronic acid (1 mmol), (0.3 mol%) of catalyst in 5 mL of MeCN: H₂O (4:1), TEA (0.64 mL, 5.0 mmol) were added to the reaction mixture, the mixture was stirred at room temperature under blue light.

Hydroxylation reaction catalysed by Co(II)TCPP supported on polyaniline.

A mixture of (0.3 mol%) of Co(II)TCPP and (0.3 mol%) of prepared polyaniline were stirred for 15 min in 5 mL of MeCN: H₂O (4:1) at pH 9 using NaOH solution till completely adsorption of catalyst on polyaniline surface, arylboronic acid (1 mmol) and TEA (0.64 mL, 5.0 mmol) were added to the reaction mixture, the mixture was stirred at room temperature under blue light.

Q11. Some references were missed:

DOI: 10.1021/ja406311g

DOI: 10.1039/C8QO00061A

DOI: 10.1021/acs.joc.7b00487

DOI: 10.1039/c5cc01519g

DOI: 10.1039/c3ob42081g

DOI: 10.1002/anie.201107028

DOI: 10.3762/bjoc.16.83

A11. These reference suggested by the referee were cited as references No. 8,10,11,12,13,14 and 25 in the revised version.

Q12. Please add emission profile of the light source used for irradiation of the reaction mixture

A12. Kessil A160WE Tuna Blue (523 nm) used as source of visible light for the hydroxylation reaction. This sentence was added to the text and supporting information in the revised version.

Author Response File: Author Response.pdf

Reviewer 3 Report

This manuscript deals with the oxidative hydroxylation of aryl boronic acids catalyzed by Co-porphyrins supported onto PANI or chitosan under blue-light irradiation. In particular, the cobalt (II) meso-Tetraphenylporphyrin Co(TPP) and cobalt (II) 5,10,15,20-Tetrakis(4-carboxyphenyl)porphyrin Co(TCPP) were immobilized on the supporting polymers. These catalysts were used in order to promote the hydroxylation of phenyl boronic acids to form phenol derivatives under various reaction conditions.

Specific comments are following reported:

The reaction conditions were optimized by using phenylboronic acid as starting material and PANI as supporting polymer; just an example (see entry 13, Table 1) is referred to chitosan. The reporting of more examples using chitosan instead of PANI is suggested (e. g. could be added in Table 2).
The captions of Table 1 and Table 2 should be corrected (e.g. eq. 3 reports Co-TPP/PANI; but the caption reports Co-TCPP/PANI). Please check!
Are aryl boronic acids used in this work commercial products?
The authors have used the blue light to promote the reaction. Could sunlight or visible light promote the reaction?
Why did the authors choose Co (II) as metal centre? …. Why not Cu(II)?
Take into account that Cu(II) is easily also coordinated in the core of porphyrin ring for this reason it is a good candidate to catalyse these reactions (see Refs 7 and 8 of this work) and Muhammad, M. H., Chen, X. L., Liu, Y., Shi, T., Peng, Y., Qu, L., & Yu, B. Recyclable Cu@C3N4-Catalyzed Hydroxylation of Aryl Boronic Acids in Water under Visible Light: Synthesis of Phenols under Ambient Conditions and Room Temperature. ACS Sustainable Chemistry & Engineering, 2020, 8(7), 2682-2687.
The reusability of the catalyst is very important for the sustainability of the catalytic process . Could the authors give more details on this issue?
There is misprint a misprint at the begin of the conclusion section “Co(II)TCPP and Co(II)TCPP immobilized….”
Remark in the conclusion section that in this work PANI is more investigated than chitosan as support for porphyrin systems.
Avoid to use the same sentences in the abstract and conclusions (e.g. “This catalytic system can be used as an eco-friendly oxidation process that does not release oxidizing agents into the atmosphere”)

In the light of these considerations, publication of this work in form of research paper could be suggested after opportune revision.

Author Response

Reviewer 3:

Specific comments are following reported:

Q1. The reaction conditions were optimized by using phenylboronic acid as starting material and PANI as supporting polymer; just an example (see entry 13, Table 1) is referred to chitosan. The reporting of more examples using chitosan instead of PANI is suggested (e. g. could be added in Table 2).

A1. Although the hydroxylations of phenyl boronic acid proceeded efficiently by using Co(II)TCPP/PANI and Co(II)TCPP/Cts in high yields, the isolation of the product for homogenous Co(II)TCPP/Cts complex is very difficult. Heterogeneous system gave higher yield and easier isolation, so the further studies were undertaken by using Co(II)TCPP/PANI catalytic system. These sentences were added to the revised manuscript. (line 124-128)

Q2. The captions of Table 1 and Table 2 should be corrected (e.g. eq. 3 reports Co-TPP/PANI; but the caption reports Co-TCPP/PANI). Please check!

A2. “Co-TPP/PANI” in eq. 3 was corrected to “Co-TCPP/PANI” in the revised manuscript.

Q3. Are aryl boronic acids used in this work commercial products?

A3. Aryl boronic acids are commercially available. Phenyl boronic acid was purchased (Wako) and used without further purification. 1-Naphthalene boronic acid, 4-formyl benzene boronic acid, 4-tolyl benzene boronic acid and 4- bromo benzene boronic acid were purchased (Oakwood Chemical) ) and used without further purification. 2,4,6-Trimethylphenyl boronic acid (Tokyo Kasei) was purchased and used without further purification. These contents were added to the supporting information in the revised version.

Q4. The authors have used the blue light to promote the reaction. Could sunlight or visible light promote the reaction?

A4. These collected results suggest that photosensitizer, blue light, and atmospheric air are essential for the reaction. No reactions proceeded under nitrogen atmosphere and in the absence of blue-light (Table1 entries 14 and 15). As the porphyrins absorb intensely in the Soret region (around 435 nm) and partially in the Q region (around 600nm) we carried out all hydroxylation reaction under blue LED light (435−600 nm). These sentences were added to the revised text. (line 134-138)

Q5. Why did the authors choose Co (II) as metal centre? …. Why not Cu(II)?
Take into account that Cu(II) is easily also coordinated in the core of porphyrin ring for this reason it is a good candidate to catalyse these reactions (see Refs 7 and 8 of this work) and Muhammad, M. H., Chen, X. L., Liu, Y., Shi, T., Peng, Y., Qu, L., & Yu, B. Recyclable Cu@C3N4-Catalyzed Hydroxylation of Aryl Boronic Acids in Water under Visible Light: Synthesis of Phenols under Ambient Conditions and Room Temperature. ACS Sustainable Chemistry & Engineering, 2020, 8(7), 2682-2687.

A5. Co(II)porphyrin was chosen as a good catalyst because it has a higher ability to bind towards O₂ in aqueous solution besides the stability and long lifetime phosphorescence compared to Cu(II) that has a far shorter lifetime phosphorescence. This sentences wad added to the revised text. (line 43-45)

Q6. The reusability of the catalyst is very important for the sustainability of the catalytic process. Could the authors give more details on this issue?

A6. Re-use of the catalyst Co(II)TCPP supported on polyaniline was tested as follows. Hydroxylation of phenylboronic acid was carried out under standard conditions of Table 1, after the completion of the first run the solvent was removed by filtration and the product was isolated and determined by NMR measurements. The precipitate (Co-porphyrin supported on polyaniline) could be washed with water and used for the second time by added the initial amount of phenylboronic acid, TEA and solvent, then the reaction was carried out at room temperature for 6 h to give 40 % of the product. After two runs we found that the re-use of the catalyst activity is less than the fresh catalyst. The deactivation of the catalyst could be due to the accumulation of the reaction products and porphyrin in the polymer. Although we couldn’t find a practical re-usable catalytic method, we improve the yields by finding suitable solvent for isolating the product and these results would be disclosed as a full paper in near future.

Q7. There is misprint a misprint at the begin of the conclusion section “Co(II)TCPP and Co(II)TCPP immobilized….”

A7. “Co(II)TCPP” was removed in accord with reviewer’s comment.

Q8. Remark in the conclusion section that in this work PANI is more investigated than chitosan as support for porphyrin systems.

A8. The immobilized porphyrins on polyaniline were more investigated because improving the stability by site isolation which prevent porphyrin aggregation and intermolecular self-oxidation. This sentences was added to the conclusion in the revised version.

Q9. Avoid to use the same sentences in the abstract and conclusions (e.g. “This catalytic system can be used as an eco-friendly oxidation process that does not release oxidizing agents into the atmosphere”)

A9. The sentence changed to “We developed an eco-friendly reaction for the hydroxylation of phenyl boronic acid that doesn’t require as the oxidizing agents”, in the revised version. (line 298-299)

Author Response File: Author Response.pdf

Reviewer 4 Report

In this work Kimura and Atia described an intresting oxidation procedure capable to afford phenols starting from ariyl boronic acids. The manuscript is well written and the methods carefully described. I recommand the publication of this work on Catalyst after addressing some minor points:

I think the authors have to spend a few words for in the introductive section for describing the preparation of aryl boronic acids (and provide some literature).

The conclusions are too short and must be expanded.

Author Response

Reviewer 4:

Q1. I think the authors have to spend a few words for in the introductive section for describing the preparation of aryl boronic acids (and provide some literature).

A1. We added the sentences and references in the revised version. Additionally written changes are highlighted in yellow background of the revised introduction. (line 29-32)

Q2. The conclusions are too short and must be expanded.

A2. We made changed on conclusion in the revised version. The conclusion part was expanded and highlighted the changes in yellow background in the revised version. (line 298-305)

Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

The authors have opportunely revised their manuscript.

The manuscript that can be accepted for publication.